Pyrexia (fever) is common to all mammals, including equines such as horses. Pyrexia is an elevation in core body temperature above the normal range due to an increase in the temperature regulatory set-point. Pyrexia can be caused by many medical conditions ranging from non-serious to potentially serious and even life threatening. These include viral, bacterial, and parasitic infections, such as equine encephalomyelitis, equine influenza, equine herpes virus, West Nile virus, strangles, and Potomac horse fever. Physical trauma and stress can also cause a fever in a horse. While a fever can be a useful defense mechanism, since the body's immune response can be strengthened at higher temperatures, very high body temperatures, particularly for prolonged periods of time, can pose significant health risks to the patient. In the setting of animal and human healthcare, it often becomes necessary to reduce a patient's temperature to a safer range (e.g., treat the patient's fever) by medical intervention. Some of the most common causes of illness in horses are febrile diseases, such as respiratory infections, certain forms of colic, post-vaccination reactions, and tick- and mosquito-borne infections).
The treatment of pyrexia in horses and foals by parenteral administration of the nonsteroidal anti-inflammatory drug (NSAID) metamizole is known in the art. Metamizole products are marketed in some countries under the generic name dipyrone and a variety of brand names including, but not limited to Vetalgin® as an antipyretic, analgesic, and anti-inflammatory agent. Currently available veterinary formulations of metamizole require parenteral (i.e., intramuscular, intravenous (IV), or subcutaneous) administration, with IV administration being the usual route. The oral formulations of metamizole available in the veterinary market for dogs are not suitable for administration to horses due to a variety of factors including dose. Obtaining an oral dosage form of metamizole of sufficiently high concentration to treat a large animal such as a horse is itself technically challenging, but to further do so (i) in an oral format that facilitates the horses actually ingesting the drug as opposed to expelling it from the mouth prior to ingestion, and (ii) in an oral format that is stable at the temperatures typically found in a barn environment, is even more so.
Parenteral administration of metamizole in horses presents many difficulties, however, and there is a need for simpler methods for treating pyrexia. Horses have large jugular veins that, when healthy, are simple to access. However, other peripheral vessels are much more challenging. Access to jugular veins can be limited for numerous reasons, including but not limited to thrombosis, poor temperament, and localized dermal disease. Once the jugular veins are inaccessible, intravenous administration of medication to a horse is extremely challenging. Moreover, in some instances, an unintended peri-vascular administration of metamizole to an equine may result in adverse effects, including, but not limited to, thrombophlebitis. This is true of NSAIDs, like metamizole, generally. Further complications can arise due to, in many instances, medications being administered to horses by non-veterinary personnel. These individuals often lack the training and experience to administer parenteral medications safely. Additionally, many medications are administered repeatedly or chronically, which may lead to thrombosis of the vein. Finally, the equine patient may also develop evasive behaviors, so repeat parenteral administration of any medication can be challenging for that reason alone.
For these and other reasons, there exists an unmet need for veterinary formulations of metamizole suitable for oral administration to equines to treat pyrexia that avoid difficulties commonly known and experienced with the currently available parenteral formulations. There further exists an unmet need for oral veterinary formulations of metamizole that can be easily and readily administered to a horse, even by unskilled caretakers who are not veterinarians. Such formulations and methods for using and administering them are provided by the present disclosure.